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Thread: ChinaSCINet Update

  1. #851
    Wise how much is needed to do phase 3?

  2. #852
    wise, we see that differet foundations are getting million of dollars from differnt methods. You seem to be the most efficeint in bringing therapies to trials. Why is it that monies don't come your way? Is there amything that we can do, other than personal contributions, to help? Also, can we get to real dates on phase 3 trials for china and phase 3 trials for the USA? Is there a real chance that UCBC ANd LITHIUM WILL WORK FOR MANY OF US TO IMPROVE FUNCTION, LIKE WALKING AND BOWEL ANd BLADDER, i KNOW YOU HAVe ANSwERED SOMe OF THESE QUESTIONS BEFORE, but we need to know the truth at this time. In other words talking about 2014 just to start trials with cethrin means we are years away from any real treatment that will benefit many of us. Please be specific if you decide to answer these questions.

    anthony

  3. #853
    Quote Originally Posted by Wise Young View Post
    Everybody,

    People can ask questions and don't have to donate money to ask questions. What people don't have the right to do here on CareCure is to question somebody's honesty, integrity, motivation, intelligence, or work ethics when asking questions. That just leads to anger, erodes friendships, and causes miscommunication.

    Wise.
    ----------------------

    Paolo,

    Please be patient. I have been writing an answer to your question and it is taking more time than I had thought. I should have posted that I will be answering part of your question. By the way, please do not expect me to present detailed data about our study and you simply will have to wait until we have it accepted for publication before I present such data.

    Wise.

    Magnetic resonance diffusion tensor imaging (MR-DTI)

    Magnetic resonance diffusion tensor imaging (MR-DTI) is a method of analyzing magnetic resonance data so that it shows water diffusion. As you know, standard magnetic resonance detects water (H2O). Water is the most abundant molecule in biological tissues and excitation of H2O by pulses of electromagnetic energy in a strong magnetic field will perturb the molecule so that it emits energy back in a specific frequency. Movement of water produces changes of magnetic resonance in sequential snapshots of the tissue. Normally, in non-oriented tissues, water diffuses in all directions. However, in oriented tissues, the diffusion will be more restricted in some directions than others. This property is called anisotrophy.

    White matter is the most oriented tissues in the central nervous system, containing bundles of fibers running longitudinally for long distances. Also called diffusion MRI (dMRI), MR-DTI has been used for mapping diffusion in brain tissues since the early 1980's. During the last 25 years, it has been applied to many neurological conditions and has served as the basis of the Human Brain Connectome project, which is building maps of anatomical and functional connections of the human brain. Many studies have now been published on MR-DTI of spinal white matter. For example, a search "diffusion tensor imaging" and "spinal cord" on Google Scholar yielded over 150 published articles on the subject.

    Software is now available for a user to select an area of interest (i.e. white matter above the injury site or below the injury site) and the program will find contiguous tissues that show the same directional diffusion characteristics. In other words, the software will show bundles of oriented fibers that are contiguous with each other. By doing so, we can see the white matter above the injury site and below the injury site. If any white matter tracts were to regrow across the injury site, we should be able to see them cross the injury site. So, we used MR-DTI in our trial to identify the injection sites (at the white matter wave fronts rostral and caudal to the injury site) and to detect white matter growth across in the injury site. The degree and volume anisotrophy can be quantified to assess white matter change.

    Mulcahey, et al. [1] at Shriner’s hospital recently examined the DTI images of children with spinal cord injury. They found good-to-strong reliability on repeated scans and moderate-to-good concurrent validity with clinical (ASIA) classifications of the injury. They concluded that DTI is a better predictor of clinical findings (i.e. AIS A, B, C, D, E) than conventional MRI. Freund, et al. [2] imaged nine adult volunteers with cervical spinal cord injury and found significant differences of corticospinal tract of SCI subjects compared to controls, including ability to predict paralysis of different parts of the body. Bosma & Stroman [3] reviewed studies using DTI to visualize spinal cords in patients with amyotrophic lateral sclerosis, myelitis, and spinal cord tumors. Smith, et al. [4] at Kennedy Krieger in Baltimore reported that DTI images can reliably discriminate sensory and motor tracts. Ellington, et al. [5] compared four subjects with spinal cord injury with 4 normal subjects. They found a general decrease in both longitudinal and transverse diffusivity in the former.

    Many investigators have used DTI to investigate animal models of spinal cord injury. Tu, et al. [6] at Washington University in St. Louis used DTI to quantify spared white matter in mice after contusion injuries. Sundberg, et al. [7] used DTI to assess rats at various times up to 56 days after contusion injuries. White matter in regions up to a centimeter from the injury site showed significant changes that were not seen on conventional MRI. Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate. Ellingson, et al. [11] found that both transverse and longitudinal diffusivity (tADC and lADC), as well as mean diffusivity (MD) and fractional anisotrophy (FA), changed over time in rodents after injury.

    Nobody has looked at human spinal cords before and after cell transplants, or changes in white matter associated with transplants. Therefore, we planned such a study in Hong Kong. It was a very difficult study because the presence of metallic implants around the injury site distorted the images and introduced artifacts. Most patients have such metallic implants. Also, we had to work out many issues, including the parameters that would be used for imaging the white matter. We hypothesized that subjects with “complete” ASIA A spinal cord injuries would not have any white matter crossing the injury site, that injections of small amounts of cells (i.e. 4 and 8 ┬Áliters) would not change the white matter in the spinal cord, and that restoration of function would be associated with appearance of white matter bundles crossing the injury site. So, we did a study of MR-DTI images of 8 subjects with chronic SCI before and at 6 weeks, 6 months, 12 months (and 18 months) after transplantation umbilical cord blood mononuclear cells (four injections of 4 or 8 ┬Áliters) in the spinal cord above and below and injury site. These are compared with 8 normal control subjects.

    This will be the subject of the study that we will soon submit for publication.

    References Cited

    1. Mulcahey MJ, Samdani A, Gaughan J, Barakat N, Faro S, Betz RR, et al. Diffusion tensor imaging in pediatric spinal cord injury: preliminary examination of reliability and clinical correlation. Spine (Phila Pa 1976). 2012;37(13):E797-803.
    2. Freund P, Wheeler-Kingshott CA, Nagy Z, Gorgoraptis N, Weiskopf N, Friston K, et al. Axonal integrity predicts cortical reorganisation following cervical injury. J Neurol Neurosurg Psychiatry. 2012;83(6):629-37. PMCID: 3348614.
    3. Bosma R, Stroman PW. Diffusion tensor imaging in the human spinal cord: development, limitations, and clinical applications. Crit Rev Biomed Eng. 2012;40(1):1-20.
    4. Smith SA, Jones CK, Gifford A, Belegu V, Chodkowski B, Farrell JA, et al. Reproducibility of tract-specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla. NMR Biomed. 2010;23(2):207-17. PMCID: 2830283.
    5. Ellingson BM, Ulmer JL, Schmit BD. Morphology and morphometry of human chronic spinal cord injury using diffusion tensor imaging and fuzzy logic. Ann Biomed Eng. 2008;36(2):224-36.
    6. Tu TW, Kim JH, Wang J, Song SK. Full tensor diffusion imaging is not required to assess the white-matter integrity in mouse contusion spinal cord injury. J Neurotrauma. 2010;27(1):253-62. PMCID: 2824236.
    7. Sundberg LM, Herrera JJ, Narayana PA. In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury. J Neurotrauma. 2010;27(10):1753-67. PMCID: 2992395.
    8. Kim JH, Loy DN, Wang Q, Budde MD, Schmidt RE, Trinkaus K, et al. Diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long-term locomotor recovery. J Neurotrauma. 2010;27(3):587-98. PMCID: 2867549.
    9. Kim JH, Tu TW, Bayly PV, Song SK. Impact speed does not determine severity of spinal cord injury in mice with fixed impact displacement. J Neurotrauma. 2009;26(8):1395-404. PMCID: 2850293.
    10. Herrera JJ, Chacko T, Narayana PA. Histological correlation of diffusion tensor imaging metrics in experimental spinal cord injury. J Neurosci Res. 2008;86(2):443-7.
    11. Ellingson BM, Kurpad SN, Schmit BD. Ex vivo diffusion tensor imaging and quantitative tractography of the rat spinal cord during long-term recovery from moderate spinal contusion. J Magn Reson Imaging. 2008;28(5):1068-79.
    Wise,

    thanks for this long explaination. It actually confirmed what I knew about DTI and I learned some more.
    If I interpret correctly the following:
    Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate.

    it means that you can't decetc AXONS growing accros the injury site using a DTI as you seem to suggest in your presentation.
    The change a DTI can show might be due just to remyelination of intact axons.

    In any case I look forward with much interest to the publication with the DTIs.

    Paolo
    Last edited by paolocipolla; 06-17-2012 at 09:13 PM.
    In God we trust; all others bring data. - Edwards Deming

  4. #854
    Few thousands regular viewers of this thread and few thousands regular contributors to "just a dollar please" will not make a difference.
    We need to hire professionals to raise serious money!
    Thinking outside of box people...
    Something as http://www.kickstarter.com
    or
    Nike or Adidas sponsorship (Impossible is nothing or Just do it fits perfectly : )
    or
    going out to main stream media with truth and appeal for help
    or
    ask Paolo how to proceed

    whatever is needed ... better than stall in this flight in this crucial moment,
    just need a team to prepare
    www.MiracleofWalk.com

    Miracles are not contrary to nature, but only contrary
    to what we know about nature
    Saint Augustine

  5. #855
    Quote Originally Posted by paolocipolla View Post
    Wise,

    thanks for this long explaination. It actually confirmed what I knew about DTI and I learned some more.
    If I interpret correctly the following:
    Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate.

    it means that you can't decetc AXONS growing accros the injury site using a DTI as you seem to suggest in your presentation.
    The change a DTI can show might be due just to remyelination of intact axons.

    In any case I look forward with much interest to the publication with the DTIs.

    Paolo
    If there were no anisotropy at the injury site before treatment, i.e. a gap, and then significant bundles of anisotropic white matter appears after the treatment, going long distances across the injury site and beyond, that would be a pretty strong argument for regeneration, don't you think?

    Wise.

  6. #856
    Quote Originally Posted by moneymaker View Post
    Wise how much is needed to do phase 3?
    I am estimating that it will require about US$4 million in China and US$12 million in the U.S. Wise.

  7. #857
    Senior Member muskie's Avatar
    Join Date
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    Red Bull is a sponsor of SCI related projects, just a thought if you were looking for a big corporate sponsor.
    Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

  8. #858
    Quote Originally Posted by muskie View Post
    Red Bull is a sponsor of SCI related projects, just a thought if you were looking for a big corporate sponsor.
    Thanks, I will ask Jim Bennett to look into this. Wise.

  9. #859
    Senior Member
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    Red Bull are also working with Wings for Life, see more here https://www.facesforcharity.com/en/home.html

  10. #860
    this is small as compared what the Reeve foundation and the CIRM is getting. this seems out of kilter as to relevancy. I'm thinking if your trials show any efficay, money should be directed to you. Just my thoughts.

    Anthony

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